Thermal cycling applications are an integral part of contemporary molecular biology. For example, the polymerase chain reaction (PCR), which is used to amplify nucleic acids, uses a series of DNA melting, annealing, and polymerisation steps at different temperatures to greatly ‘amplify’ the amount of DNA in a sample. Other thermal cycling applications are also known.
A typical thermal cycling apparatus consists of a metal sample block containing an appropriate number of recesses to receive one or more reaction vessels. The sample block may be shaped to conform to a 96-well plate format or individual reaction-tubes that are generally 0.5 μl or 0.20 micro-centrifuge (Eppendorf) tubes. The metal block acts as a thermal mass that transfers its thermal energy to and from the reaction samples. In general thermal cycling energy is provided using a Thermoelectric Cooling (TEC) device, also commonly known as a Peltier Effect element (PE). A thermal cycling apparatus will generally also use a heat sink to assist in heat transfer to and from the Peltier and a large fan or the like, to remove the excess heat generated by the Peltier and transferred to the heat sink during cooling.
Peltier elements are solid-state devices that convert an electric current into a temperature gradient. They consist of two sides—a hot side and a cold side. The module acts as a heat pump in that it moves heat from the cold side to the hot side. Switching the direction of current flow will swap the hot and cold side states and regulating this current flow is used to cycle temperature of the sample block in order to provide the heating and cooling required for PCR. The hot side of the Peltier requires a method of removing that heat for the unit to function properly and to cool effectively. The more efficient the means of removing this heat from the hot side, the colder the cold side will operate and the more quickly the cold side will reach its optimum temperature for thermal transfer. This is limited by the mass of the heat sink used and the airflow of the fan used to remove the excess heat from the heat sink. In general a thermal cycler design becomes a compromise between the power rating for a specific heat sink, and the size of the heat sink and fans that can be accommodated in the design. In standard Peltier block thermal cyclers, the heat sink and fan units represent the majority of the unit and mass of the device.
Although convenient, such thermal cyclers suffer from a number of disadvantages. Key among these is that a Peltier element suffers from reduced efficiency when being used for both heating and cooling—for example, the Peltier device has significant thermal mass in the form of a heat sink which must itself be heated or cooled to enable efficient thermal transfer to the sample block. Achieving a reasonable efficiency for both heating and cooling is complex, and most thermal cycler designs must find a compromise between the heating and cooling functions of the Peltier element and the desired rate of thermal transfer to the sample block. As a consequence of this compromise, conventional thermal cyclers typically achieve a maximum heating or cooling rate of no more than 3 degrees Celsius per second and have a high power overhead to achieve these modest rates of performance.
The present invention provides an alternative thermal cycler arrangement.